Application of electric pulses, at field intensities of a few kV/cm and duration in the microsecond range has been shown to create "pores" in red cell membranes. Research is proposed to extend these observations to: 1. Define conditions in which the size of pores, or membrane permeability to molecules of differing size can be controlled. 2. Define conditions in which the leaky membranes of voltage-treated erythrocytes can be effectively resealed while the cells are prevented from hemolysis. 3. Search for specific sites of pore formation. 4. Employ this method for studying membrane structure, cation permeation, and transmembrane potential mediated molecular release. 5. Explore possible medical applications, e.g. using intact erythrocytes as intravenous drug reservoirs or carriers to maintain or prolong drug levels in a patient's circulation. 6. Develop physical models to assess various effects of voltage pulsations and to explain the observed hemolysis. Research is also proposed to undertake differential scanning microcalorimetric studies of lipid-protein, lipid-cholesterol, lipid-anesthetic interactions, and thermally induced helix-to-coil transition of myosin fragments, especially the melting transitions of subfragment-2. Thermal analysis of the molecular interactions in lipid membrane is designed to clarify the nature of the cooperativity in the bilayer structure. Calorimetric study of the thermal transitions of myosin fragments will provide energetics essential to the elucidation of mechanisms of the muscle contraction.